Brain-immune interactions: implication for cognitive impairments in Alzheimer's disease and autoimmune disorders

Abstract

Abstract Progressive memory loss and cognitive dysfunction, encompassing deficits in learning, memory, problem solving, spatial reasoning, and verbal expression, are characteristics of Alzheimer's disease and related dementia. A wealth of studies has described multiple roles of the immune system in the development or exacerbation of dementia. Individuals with autoimmune disorders can also develop cognitive dysfunction, a phenomenon termed “autoimmune dementia.” Together, these findings underscore the pivotal role of the neuroimmune axis in both Alzheimer's disease and related dementia and autoimmune dementia. The dynamic interplay between adaptive and innate immunity, both in and outside the brain, significantly affects the etiology and progression of these conditions. Multidisciplinary research shows that cognitive dysfunction arises from a bidirectional relationship between the nervous and immune systems, though the specific mechanisms that drive cognitive impairments are not fully understood. Intriguingly, this reciprocal regulation occurs at multiple levels, where neuronal signals can modulate immune responses, and immune system–related processes can influence neuronal viability and function. In this review, we consider the implications of autoimmune responses in various autoimmune disorders and Alzheimer's disease and explore their effects on brain function. We also discuss the diverse cellular and molecular crosstalk between the brain and the immune system, as they may shed light on potential triggers of peripheral inflammation, their effect on the integrity of the blood-brain barrier, and brain function. Additionally, we assess challenges and possibilities associated with developing immune-based therapies for the treatment of cognitive decline.